It is proposed to characterize and study the properties of the several deoxyribonucleases which have been obtained from the purified nuclei of HeLa cells. Nuclear DNases are thought to participate in the replication and repair of nuclear DNA, and therefore the properties of these enzymes should help to elucidate the mechanisms of DNA biosynthesis. The properties and relative activities of nuclear DNases will be compared in normal cells, neoplastic cells and cells cultured from individuals with pathological entities such as Xeroderma pigmentosum, Fanconi's anemia, Bloom's syndrome, etc., in order to ascertain if these enzymes are altered during neoplastic transformation and in conditions where DNA repair is defective. These enzymes will be purified from cultured human cells, and their activity studied in different phhases of the cell cycle and after treatment with cytotoxic agents and cancer therapeutic drugs. These experiments will be extended to studies of nuclear DNases in normal liver, in regenerating liver following partial hepatectomy, and in different grades of hepatoma.